Angiotensin-II activation of cAMP and corticosterone production in bovine adrenocortical cells: Effects of nonpeptide angiotensin-II antagonists

William E. Rainey, E. William Byrd, Rula A. Sinnokrot, Bruce R. Carr

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The ability of angiotensin-II (A-II) to increase cAMP production in adrenocortical cells is not widely accepted due to numerous conflicting reports. The recent observation that rat adrenal cells exhibit multiple subtypes of A-II receptors raises the possibility that a specific subtype could be responsible for controlling cAMP stimulation. In the present study we characterize in detail the effects of A-II on cAMP production in bovine adrenocortical zona fasciculata cells (BAC) cells and determined which A-II receptor subtype is responsible for stimulating both cAMP production and steroidogenesis. A-II (100 nM) increased the medium content of cAMP by 5- to 10-fold. The magnitude of A-II stimulation, while significant, was considerably less than that observed following treatment with ACTH (100 nM) (10-fold vs. 500-fold). The A-II stimulation of cAMP was both concentration and time dependent with a significant increase in cAMP observed in the presence of 1 nM A-II and a maximal response observed using 100 nM A-II. Stimulation was also seen using the decapeptide, A-I, and the heptapeptide, A-III. Of the angiotensin analogues tested, the order of potency was A-II > A-III > A-I. The A-II antagonist, [Sar1, Ala8]-A-II (saralasin), reversed the stimulatory effect of A-II. The superior potency of A-II and the ability of saralasin to inhibit cAMP production suggest a specific receptor mediated mechanism. In order to determine which A-II receptor subtype was responsible for stimulating cAMP, we performed experiments using the nonpeptide A-II antagonists DuP-753 and PD-123319 which are specific antagonists for A-II receptor subtypes AT1 and AT2, respectively. DuP-753 (10-10,000 nM) caused a concentration dependent inhibition of A-II (100 nM) stimulation of corticosterone and cAMP production. PD-123319 did not affect the level of either corticosterone or cAMP production in response to A-II. These results give additional support toward the ability of A-II to stimulate BAC cell cAMP production. Furthermore, the A-II stimulation of cAMP and corticosterone synthesis is regulated by the AT1 receptor subtype.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume81
Issue number1-3
DOIs
StatePublished - Oct 1991

Keywords

  • (Bovine)
  • Adrenocortical cell
  • Angiotensin-II
  • Corticosterone
  • Cyclic AMP
  • Nonpeptide angiotensin-II antagonist

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Angiotensin-II activation of cAMP and corticosterone production in bovine adrenocortical cells: Effects of nonpeptide angiotensin-II antagonists'. Together they form a unique fingerprint.

Cite this